Chemistry Reference
In-Depth Information
[Pd(SIPr)(cin)Cl] (7)
(0 .01 - 0 .1 mol%)
Br
R
HetAr
H
+
HetAr
R
K
2
CO
3,
DM A
PivOH (3 0 mol%)
1 40°C, 16 h
F
N
S
S
S
N
89%
77%
76%
90%
F
OMe
CHO
S
S
S
52%
70%
37%
Scheme 4.55 Direct arylation of heterocycles at
low catalyst
loadings using
[Pd(SIPr)(cin)Cl] (7).
4.3.5 Arylation of Ketones
The palladium-catalysed a-arylation of ketones is an elegant and effective
method to form sp
2
-sp
3
bonds.
156
In fact, no tin, zinc or boron derivative is
required as a transmetallating reagent. Indeed, in the presence of a base, the
enolate that is formed in the reaction medium can act as a suitable pseudo-
transmetallating agent. The reactivity of Pd-NHC precatalysts in the reaction
has hardly been investigated. In this section, we discuss the main achieve-
ments in the field prior to and after the award of the 2010 Nobel Prize in
Chemistry.
In 2002, Nolan and co-workers were among the first to investigate the use
of a Pd-NHC system in the a-arylation of ketones.
157
The reactivity of several
[Pd(NHC)(allyl)Cl] complexes was investigated in the reaction between
chlorobenzene and propiophenone. After optimization, the best conditions
were found to be the use of 1 mol% of [Pd(SIPr)(allyl)Cl] as the precatalyst,
NaOtBu as the base, in THF (Scheme 4.56). The scope of the reaction was
studied and the coupling of various deactivated and activated aryl chlorides,
bromides and triflates with a wide range of aryl and alkyl ketones was suc-
cessfully achieved. Notably in some cases, because the system is highly re-
active, the presence of bis-arylated products was observed. The use of bulky
aryl chlorides allowed this issue to be circumvented.
In 2005, Singh and Nolan investigated the use of a new well-defined
complex in the reaction, [Pd(IPr)(OAc)
2
](80, Scheme 4.57).
158
The system
proved highly active for the coupling of various deactivated and activated
chlorides with aryl and cyclohexyl ketones. More interestingly, 80 allowed
this kind of coupling to be performed at room temperature for the first time.
Nolan's group next continued to screen alternative throwaway ligands to
promote the reaction and thus developed palladacycle [Pd(IPr)(dmab)Cl] (81,
Table 4.25) (dmab = N,N-dimethylaminobiphenyl).
159
The a-arylation re-
action was highly successful and the catalyst loading could be decreased to
0.25 mol% in refluxing THF using NaOtBu as the base. Moreover, it was
Search WWH ::
Custom Search